A Possible Role of R Plasmids in Bacterial Permeability for β‐Lactam Antibiotics

Abstract

Four strains of clinical isolates of Serratia marcescens (13039, 13090, 13093, 14093) harboring R plasmids were highly resistant to ampicillin (ABPC) and cephaloridine (CER). With elimination of R plasmids from these strains by acriflavine treatment, ABPC-resistance levels of these strains were markedly reduced. Reduction of CER-resistance levels was also demonstrated in strains 13039 and 13093, but not in strains 13090 and 14093. The permeability of the former strains for CER was also decreased, but not in the latter strains. At the same time, fllactamase activity of these strains also almost completely disappeared when the R plasmids were eliminated. By broth matings with these strains, the recipient strains of S. marcescens 13031 (rif), Escherichia coli K-12 (rif), and E. coli 15046 (rif) all acquired a high permeability barrier against CER with inheritance of the R plasmids from strains 13039 and 13093, but not from strains 13090 and 14093. The transconjugant of strain 13031 that inherited R plasmid 13093 was resistant not only to CER but also to cefazolin, cephalothin, and cephalexin. Its permeabiiity to these antibiotics was significantly lower than that of the original strain. This fact suggests the possibility that the R plasmid from strain 13093 may be involved not only in production of p-lactamases, but also in regulation of bacterial permeability for cephalosporins.

Distribution of R Plasmids Conferring a Permeability Barrier to Cephalosporins on Bacteria Isolated from Clinical Specimens

“…Furthermore, this plasmid confers little resistance to CER and the MIC values of this antibiotic were unchanged when the plasmid was present (2). In contrast, the R plasmids in our study affected the permeability of recipients for cephalosporins but not for penicillins (9), and conferred resistance to cephalosporins including CER. Although it is still uncertain whether ,B-lactamase itself may function as a mediator of permeability regulation or not, it is likely to cause synergistical elevation of the level of resistance to CER in association with another factor conceivably contributing to alteration of bacterial cell membranes.…”

“…The hydrolytic activity of ,B-Iactamase from each strain with and without inductive treatment was iodometrically assayed by the method of Perret (15). The detailed methods were described in the previous report (9).…”

“…We also found some resistant mutants among clinical isolates of Serratia marcescens, whose permeability for cephalosporins was altered. They all carried R plasmids which conceivably influenced their permeability to cephalosporins (9). Since we have an interest in the distribution of this kind of R plasmid in clinical isolates, we made a survey of its distribution in clinical isolates of several species of bacteria.…”